The prime objective of this project is to develop an understanding of the fundamental solution chemistry of metal ions utilized in radioimmunotherapy, especially bismuth and lead. To accomplish this objective, we need to understand the coordination chemistry of the metal ions and, in particular, their kinetic and thermodynamic behaviors in aqueous solutions. This information may be used to develop radiolabeled monoclonal antibody (Mab) systems and to assess the factors which control the retention of the metal ions bound to Mab conjugates in vivo. Two systems investigated during the past year were: 1 . Pb(II) Reactions with DOTA (H4DOTA = 1.4.7,10- Tetraazacyclododecane-N.N'.N".N"'-tetraaceticacid). The rates of formation of the 1:1 complexes of Pb(DOTA)2-were studied by stopped-flow spectrophotometric techniques. The empirical form of the rate law was found to be: rate = a[Pb(II)] [DOTA]/1+b[Pb(II)] at constant acidity and [Pb]total>>[DOTA]total. A mechanism consistent with this result is the fast formation of a PB(DOTA) intermediate which rearranges during the rate-limiting-step. This kinetic information was successfully applied in the preparation of Pb-203 Mab conjugates of the Mab B72.3-DOTA. In collaborative studies described elsewhere, the biodistribution and images of these conjugates were obtained in tumor bearing mice.